Usual Adult Dose for Chronic Myelogenous Leukemia

Chronic phase: 400 mg orally once a day
Accelerated phase or blast crisis: 600 mg orally once a day

A dose increase may be considered in the absence of a severe adverse drug reaction and severe non-leukemia related neutropenia or thrombocytopenia in the following circumstances: disease progression (at any time), failure to achieve a satisfactory hematologic response after at least 3 months of treatment, failure to achieve a cytogenetic response after 6 to 12 months of treatment, or loss of a previously achieved hematologic or cytogenetic response:

• Disease progression chronic phase: 600 mg orally once a day
• Disease progression accelerated phase or blast crisis: 400 mg orally 2 times a day

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Uses:

• Newly diagnosed patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+CML) in chronic phase
• Patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+CML) in blast crisis (BC), accelerated phase (AP), or in chronic phase (CP) after failure of interferon-alpha therapy

Usual Adult Dose for Acute Lymphoblastic Leukemia

600 mg orally daily

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Use: For relapsed or refractory Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL)

Usual Adult Dose for Myeloproliferative Disorder

400 mg orally once a day

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Comments:

• Determine PDGFRb gene rearrangements status prior to initiating therapy.

Use: For patients with myelodysplastic/myeloproliferative (MDS/MPD) diseases associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements

Usual Adult Dose for Myelodysplastic Disease

400 mg orally once a day

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Comments:

• Determine PDGFRb gene rearrangements status prior to initiating therapy.

Use: For patients with myelodysplastic/myeloproliferative (MDS/MPD) diseases associated with PDGFR (platelet-derived growth factor receptor) gene rearrangements

Usual Adult Dose for Systemic Mastocytosis

• For patients with ASM without the D816V c-Kit mutation: 400 mg orally daily
• If c-Kit mutational status is not known or unavailable: 400 mg orally daily may be considered for patients with ASM not responding satisfactorily to other therapies.
• For patients with ASM associated with eosinophilia, a clonal hematological disease related to the fusion kinase FIP1L1-PDGFR alpha, a starting dose of 100 mg/day is recommended. Dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy.
• For patients with ASM associated with eosinophilia (a clonal hematological disease related to the fusion kinase FIP1L1-PDGFR alpha: 100 mg orally daily; a dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Comments:

• Determine D816V c-Kit mutation status prior to initiating treatment.

Use: For patients with aggressive systemic mastocytosis without the D816V c-Kit mutation

Usual Adult Dose for Hypereosinophilic Syndrome

• For patients with HES/CEL: 400 mg orally daily
• For patients with HES/CEL with demonstrated FIP1L1-PDGFR alpha fusion kinase: 100 mg orally daily; dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Use: For patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFR alpha fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFR alpha fusion kinase negative or unknown

Usual Adult Dose for Chronic Eosinophilic Leukemia

• For patients with HES/CEL: 400 mg orally daily
• For patients with HES/CEL with demonstrated FIP1L1-PDGFR alpha fusion kinase: 100 mg orally daily; dose increase from 100 mg to 400 mg for these patients may be considered in the absence of adverse drug reactions if assessments demonstrate an insufficient response to therapy

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Use: For patients with hypereosinophilic syndrome and/or chronic eosinophilic leukemia who have the FIP1L1-PDGFR alpha fusion kinase (mutational analysis or FISH demonstration of CHIC2 allele deletion) and for patients with HES and/or CEL who are FIP1L1-PDGFR alpha fusion kinase negative or unknown

Usual Adult Dose for Dermatofibrosarcoma Protuberans

100 mg orally daily

Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Use: For patients with unresectable, recurrent and/or metastatic dermatofibrosarcoma protuberans (DFSP)

Usual Pediatric Dose for Chronic Myelogenous Leukemia

1 year and older:
340 mg/m2 orally once a day or 170 mg/m2 orally 2 times a day
Maximum Dose: 600 mg daily
Duration of therapy: Therapy may be continued if there is no evidence of progressive disease or unacceptable toxicity.

Comments:

• Therapy can be given as a once daily dose or the daily dose may be split into 2 doses, with one portion dosed in the morning and one portion in the evening.
• There is no experience with this drug in children under 1 year of age.

Use:

• Newly diagnosed patients with Philadelphia chromosome positive chronic myeloid leukemia (Ph+CML) in chronic phase

Renal Dose Adjustments

• Mild renal impairment (CrCl 40 to 59 mL/min): Doses greater than 600 mg are not recommended.
• Moderate renal impairment (CrCl 20 to 39 mL/min): Reduce starting dose by 50% and future doses can be increased as tolerated; doses greater than 400 mg are not recommended
• Severe renal impairment (CrCl less than 20 mL/min): Caution recommended. A dose of 100 mg/day was tolerated in 2 patients in a clinical study.

Liver Dose Adjustments

• Mild or moderate hepatic impairment: No adjustment recommended.
• Severe hepatic impairment: Reduce the dose by 25%.

Dose Adjustments

Concomitant strong CYP450 3A4 inducers: This drug should not be given concomitantly with strong CYP450 3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital); if patients must be coadministered a strong CYP450 3A4 inducer the dosage of imatinib should be increased by at least 50%.

Dose Adjustment for Hepatotoxicity and Non-Hematologic Adverse Reactions: Bilirubin greater than 3 times the upper limit of normal (ULN) or in liver transaminases greater than 5 x ULN: Withhold therapy until bilirubin levels have returned to a less than 1.5 x ULN and transaminase levels to less than 2.5 x ULN. In adults, therapy may then be continued at a reduced daily dose (i.e., 400 mg to 300 mg, 600 mg to 400 mg, or 800 mg to 600 mg); in children, daily doses can be reduced from 340 mg/m2/day to 260 mg/m2/day.

If a severe nonhematologic adverse reaction develops (e.g., severe hepatotoxicity, severe fluid retention) therapy should be withheld until the event has resolved; thereafter, therapy can be resumed as appropriate depending on the initial severity of the event.

Dose adjustments for ASM associated with eosinophilia (starting dose 100 mg):
ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L:
1. Stop therapy until ANC greater than or equal to 1.5 x 10(9)/L and platelets greater than or equal to 75 x 10(9)/L.
2. Resume therapy at previous dose (i.e., before severe adverse reaction).

Dose adjustments for HES/CEL with FIP1L1-PDGFR alpha fusion kinase (starting dose 100 mg):
ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L:
1. Stop therapy until ANC greater than or equal to 1.5 x 10(9)/L and platelets greater than or equal to 75 x 10(9)/L.
2. Resume therapy at previous dose (i.e., before severe adverse reaction).

Dose adjustments for Chronic Phase CML (starting dose 400 mg):
ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L:
1. Stop therapy until ANC greater than or equal to 1.5 x 10(9)/L and platelets greater than or equal to 75 x 10(9)/L.
2. Resume therapy at the original starting dose of 400 mg.
3. If recurrence of ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L, repeat step 1 and resume therapy at a reduced dose of 300 mg.

Dose adjustments for MDS/MPD (starting dose 400 mg):
ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L:
1. Stop therapy until ANC greater than or equal to 1.5 x 10(9)/L and platelets greater than or equal to 75 x 10(9)/L.
2. Resume therapy at the original starting dose of 400 mg.
3. If recurrence of ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L, repeat step 1 and resume therapy at a reduced dose of 300 mg.

Dose adjustments for ASM (starting dose 400 mg):
ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L:
1. Stop therapy until ANC greater than or equal to 1.5 x 10(9)/L and platelets greater than or equal to 75 x 10(9)/L.
2. Resume therapy at the original starting dose of 400 mg.
3. If recurrence of ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L, repeat step 1 and resume therapy at a reduced dose of 300 mg.

Dose adjustments for HES/CEL (starting dose 400 mg)
ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L:
1. Stop therapy until ANC greater than or equal to 1.5 x 10(9)/L and platelets greater than or equal to 75 x 10(9)/L.
2. Resume therapy at the original starting dose of 400 mg.
3. If recurrence of ANC less than 1 x 10(9)/L and/or platelets less than 50 x 10(9)/L, repeat step 1 and resume therapy at a reduced dose of 300 mg.

Dose adjustments for Ph+ CML: Accelerated Phase and Blast Crisis (starting dose 600 mg):
ANC less than 0.5 x 10(9)/L and/or platelets less than 10 x 10(9)/L:
1. Check if cytopenia is related to leukemia (marrow aspirate or biopsy).
2. If cytopenia is unrelated to leukemia, reduce dose to 400 mg.
3. If cytopenia persists 2 weeks, reduce dose further to 300 mg.
4. If cytopenia persists 4 weeks and is still unrelated to leukemia, stop therapy until ANC greater than or equal to 1 x 10(9)/L and platelets greater than or equal to 20 x 10(9)/L and then resume therapy at 300 mg.

Dose adjustments for Ph+ ALL (starting dose 600 mg):
ANC less than 0.5 x 10(9)/L and/or platelets less than 10 x 10(9)/L:
1. Check if cytopenia is related to leukemia (marrow aspirate or biopsy).
2. If cytopenia is unrelated to leukemia, reduce dose to 400 mg.
3. If cytopenia persists 2 weeks, reduce dose further to 300 mg.
4. If cytopenia persists 4 weeks and is still unrelated to leukemia, stop therapy until ANC greater than or equal to 1 x 10(9)/L and platelets greater than or equal to 20 x 10(9)/L and then resume therapy at 300 mg.

Precautions

CONTRAINDICATIONS:

• None

Safety and efficacy have not been established in patients younger than 1 year.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• This drug should be taken with a meal and a large glass of water.
• Doses of 400 mg or 600 mg should be administered once daily, and a dose of 800 mg should be administered as 400 mg twice a day.
• For patients unable to swallow the film-coated tablets, the tablets may be dispersed in a glass of water or apple juice. The required number of tablets should be placed in the appropriate volume of beverage (approximately 50 mL for a 100 mg tablet, and 200 mL for a 400 mg tablet) and stirred with a spoon. The suspension should be administered immediately after complete disintegration of the tablet(s).
• For daily dosing of 800 mg and above, dosing should be accomplished using the 400 mg tablet to reduce exposure to iron.

Monitoring:

• Complete blood counts, liver function, and weight.
• Caution is recommended in patients with cardiac disease or cardiac risk factors. -Any patient with symptoms consistent with cardiac failure should be evaluated and treated as appropriate.

Frequently asked questions

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